Influence of ductility on the structural behavior of light-gage cold-formed steel members

Ductility parameters defined in the second progress report were previously obtained by conducting tension coupon tests on specially produced A and S steels. In this report, tension coupon test results are presented for a 20 gage commercial low ductility steel, i.e. an ASTM Grade E steel, herein designated as steel B. Its behavior is compared with that of the specially rolled A and S steels to test the validity of conclusions arrived at in the second progress report. Test programs were set up to study the behavior of B steel under static tension loading, one program for single bolted connections and another for rectangular plates with holes. Here again the behavior of B steel is compared with A and S steels. A few connection tests were conducted on fully annealed A steel specimens to compare their behavior with low ductility A steel specimens. In Appendix B the processing and metallurgical history for A, B and S steels is given

Long Covid symptoms and diagnosis in primary care: A cohort study using structured and unstructured data in The Health Improvement Network primary care database

BACKGROUND: Long Covid is a widely recognised consequence of COVID-19 infection, but little is known about the burden of symptoms that patients present with in primary care, as these are typically recorded only in free text clinical notes. AIMS: To compare symptoms in patients with and without a history of COVID-19, and investigate symptoms associated with a Long Covid diagnosis. METHODS: We used primary care electronic health record data until the end of December 2020 from The Health Improvement Network (THIN), a Cegedim database. We included adults registered with participating practices in England, Scotland or Wales. We extracted information about 89 symptoms and 'Long Covid' diagnoses from free text using natural language processing. We calculated hazard ratios (adjusted for age, sex, baseline medical conditions and prior symptoms) for each symptom from 12 weeks after the COVID-19 diagnosis. RESULTS: We compared 11,015 patients with confirmed COVID-19 and 18,098 unexposed controls. Only 20% of symptom records were coded, with 80% in free text. A wide range of symptoms were associated with COVID-19 at least 12 weeks post-infection, with strongest associations for fatigue (adjusted hazard ratio (aHR) 3.46, 95% confidence interval (CI) 2.87, 4.17), shortness of breath (aHR 2.89, 95% CI 2.48, 3.36), palpitations (aHR 2.59, 95% CI 1.86, 3.60), and phlegm (aHR 2.43, 95% CI 1.65, 3.59). However, a limited subset of symptoms were recorded within 7 days prior to a Long Covid diagnosis in more than 20% of cases: shortness of breath, chest pain, pain, fatigue, cough, and anxiety / depression. CONCLUSIONS: Numerous symptoms are reported to primary care at least 12 weeks after COVID-19 infection, but only a subset are commonly associated with a GP diagnosis of Long Covid

The involvement of reactive oxygen species in causing chronic cardiovascular and neurodegenerative diseases and some cancers

An increase in the occurrence of different infectious and chronic diseases as well as aging population has resulted in poor human health and decline in the quality of life all over the world. In fact, chronic diseases, which are partially resistant to currently available drugs are long lasting health hazards and require ongoing medical attention. Major causes of increase in these diseases are considered to be changes in the environment as well as diets and lifestyle. Particularly, there has been changes from a simple, nutritious, lowcalorie diet and active lifestyle to a complex and processed food rich in high calories accompanied by a sedentary lifestyle and unhealthy living habits. Since high-calorie diets and inactive lifestyle are known to promote the production of reactive oxygen species (ROS) in the body, it is likely that oxidative stress and associated inflammation may be intimately involved in enhancing the resistance of several disorders to the existing therapeutic interventions and thus promoting the occurrence of chronic diseases. A thorough review of literature regarding the pathogenesis of some major chronic diseases including cardiovascular disease like heart failure, neurodegenerative disorder like Alzheimer's disease and various types of cancer has revealed that these health hazards are associated with increased oxidative stress, production of pro-inflammatory chemicals such as nitric oxide and some cytokines, as well as formation of some toxic substances such as advanced glycation end products. It is thus evident that extensive research work by employing genetic, immunological and nutraceutical approaches, needs to be carried out for developing some novel antioxidants with anti-inflammatory activities for reducing the incidence of chronic diseases. In the meantime, it would be prudent for patients with chronic diseases to pursue the preventive measures involving reduced intake of high calorie diet and following an active lifestyl

Involvement of protein kinases associated signal transduction mechanisms in cardiac diseases

Protein kinases, a family of enzymes responsible for regulating various cellular processes, have been implicated in the development and progression of various heart diseases, making them attractive therapeutic targets. This review focuses on the role of protein kinases induced phosphorylation and protein phosphatase-induced dephosphorylation in cardiovascular disorders, including heart failure, ischemic heart disease, arrhythmias, hypertension, and diabetic cardiomyopathy. This paper explores the potential of novel kinase-targeted therapies and emerging technologies for the prevention and treatment of these conditions. It also discusses the involvement of protein kinase A (PKA), protein kinase C (PKC), phosphoinositide 3-kinases (PI3Ks), mitogen-activated protein kinases (MAPKs), and Ca2+/calmodulin-dependent protein kinase II (CaMKII) in heart dysfunction and alterations in their function that contribute to their respective cardiac disorders. Furthermore, this article presents a comprehensive overview of protein kinases in cardiac disorders and the potential of innovative kinase-targeted therapies, advanced technologies, and multidisciplinary approaches for the effective prevention and treatment of cardiovascular diseases, ultimately aiming to improve patient outcomes and quality of life

Multifrequency Photo-polarimetric WEBT Observation Campaign on the Blazar S5 0716+714: Source Microvariability and Search for Characteristic Timescales

Here we report on the results of the WEBT photo-polarimetric campaign targeting the blazar S5~0716+71, organized in March 2014 to monitor the source simultaneously in BVRI and near IR filters. The campaign resulted in an unprecedented dataset spanning $\sim 110$\,h of nearly continuous, multi-band observations, including two sets of densely sampled polarimetric data mainly in R filter. During the campaign, the source displayed pronounced variability with peak-to-peak variations of about $30\%$ and "bluer-when-brighter" spectral evolution, consisting of a day-timescale modulation with superimposed hourlong microflares characterized by $\sim 0.1$\,mag flux changes. We performed an in-depth search for quasi-periodicities in the source light curve; hints for the presence of oscillations on timescales of $\sim 3$\,h and $\sim 5$\,h do not represent highly significant departures from a pure red-noise power spectrum. We observed that, at a certain configuration of the optical polarization angle relative to the positional angle of the innermost radio jet in the source, changes in the polarization degree led the total flux variability by about 2\,h; meanwhile, when the relative configuration of the polarization and jet angles altered, no such lag could be noted. The microflaring events, when analyzed as separate pulse emission components, were found to be characterized by a very high polarization degree ($> 30\%$) and polarization angles which differed substantially from the polarization angle of the underlying background component, or from the radio jet positional angle. We discuss the results in the general context of blazar emission and energy dissipation models.Comment: 16 pages, 17 Figures; ApJ accepte

The 72-Hour WEBT Microvariability Observation of Blazar S5 0716+714 in 2009

Context. The international whole earth blazar telescope (WEBT) consortium planned and carried out three days of intensive micro-variability observations of S5 0716+714 from February 22, 2009 to February 25, 2009. This object was chosen due to its bright apparent magnitude range, its high declination, and its very large duty cycle for micro-variations. Aims. We report here on the long continuous optical micro-variability light curve of 0716+714 obtained during the multi-site observing campaign during which the Blazar showed almost constant variability over a 0.5 magnitude range. The resulting light curve is presented here for the first time. Observations from participating observatories were corrected for instrumental differences and combined to construct the overall smoothed light curve. Methods. Thirty-six observatories in sixteen countries participated in this continuous monitoring program and twenty of them submitted data for compilation into a continuous light curve. The light curve was analyzed using several techniques including Fourier transform, Wavelet and noise analysis techniques. Those results led us to model the light curve by attributing the variations to a series of synchrotron pulses. Results. We have interpreted the observed microvariations in this extended light curve in terms of a new model consisting of individual stochastic pulses due to cells in a turbulent jet which are energized by a passing shock and cool by means of synchrotron emission. We obtained an excellent fit to the 72-hour light curve with the synchrotron pulse model

FOXN1 forms higher-order nuclear condensates displaced by mutations causing immunodeficiency

The transcription factor FOXN1 is a master regulator of thymic epithelial cell (TEC) development and function. Here, we demonstrate that FOXN1 expression is differentially regulated during organogenesis and participates in multimolecular nuclear condensates essential for the factor’s transcriptional activity. FOXN1’s C-terminal sequence regulates the diffusion velocity within these aggregates and modulates the binding to proximal gene regulatory regions. These dynamics are altered in a patient with a mutant FOXN1 that is modified in its C-terminal sequence. This mutant is transcriptionally inactive and acts as a dominant negative factor displacing wild-type FOXN1 from condensates and causing athymia and severe lymphopenia in heterozygotes. Expression of the mutated mouse ortholog selectively impairs mouse TEC differentiation, revealing a gene dose dependency for individual TEC subtypes. We have therefore identified the cause for a primary immunodeficiency disease and determined the mechanism by which this FOXN1 gain-of-function mutant mediates its dominant negative effect

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types